LB0001 BIMEKIZUMAB IN BDMARD-NAIVE PATIENTS WITH PSORIATIC ARTHRITIS: 24-WEEK EFFICACY &amp; SAFETY FROM BE OPTIMAL, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED, ACTIVE REFERENCE STUDY
Authors: I. Mcinnes, L. Coates, R. B. M. Landewé, P. J. Mease, C. T. Ritchlin, Y. Tanaka, A. Asahina, L. Gossec, A. B. Gottlieb, R. B. Warren, B. Ink, D. Assudani, J. Coarse, R. Bajracharya, J. F. Merola
Journal: Annals of the Rheumatic Diseases (2022)

Background Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. Objectives Assess BKZ efficacy and safety vs PBO in bDMARD-naïve pts with active PsA to Wk 24 of BE OPTIMAL. Methods BE OPTIMAL ( NCT03895203 ) comprises 16 wks double-blind PBO-controlled and 36 wks treatment-blind. Pts were ≥18 yrs, bDMARD-naïve, with adult-onset, active PsA, ≥3 tender and ≥3 swollen joints. Pts randomised 3:2:1, subcutaneous BKZ 160 mg Q4W:PBO:adalimumab (ADA; reference arm) 40 mg Q2W. From Wk 16, PBO pts received BKZ 160 mg Q4W. Primary endpoint: ACR50 at Wk 16. Results 821/852 (96.4%) pts completed Wk 16 and 806 (94.6%) Wk 24. Mean age 48.7 yrs, BMI 29.2 kg/m 2 ; since diagnosis: 5.9 yrs; 46.8% male. BL characteristics comparable across arms. Primary endpoint met (Wk 16 ACR50: 43.9% BKZ vs 10.0% PBO, p&lt;0.001; ADA: 45.7%; Figure 1). All ranked secondary endpoints met at Wk 16 (Table 1). As early as Wk 2, ACR20 was higher in BKZ vs PBO (27.1% vs 7.8%, nominal p&lt;0.001; ADA: 33.6%). Outcomes continued to improve at Wk 24 (Table 1). To Wk 16, pts with ≥1 TEAE, BKZ: 59.9%; PBO: 49.5%; ADA: 59.3%. SAE rate low (1.6%; 1.1%; 1.4%). Most frequent (≥5%) AEs for all arms: nasopharyngitis (9.3%; 4.6%; 5.0%), URTI (4.9%; 6.4%; 2.1%), increased ALT (0.7%; 0.7%; 5.0%). Candida infections: 2.6%, 0.7%, 0%; no systemic candidiasis. 2 malignancies (BKZ: basal cell carcinoma; PBO: breast cancer stage 1); no MACE, uveitis, IBD or deaths. Table 1. Wk 16 and 24 efficacy BL Wk 16 Wk 24 PBO N=281 BKZ 160 mg Q4W N=431 ADA 40 mg Q2W N=140 † PBO N=281 BKZ 160 mg Q4W N=431 ADA 40 mg Q2W N=140 † p value (BKZ vs PBO ) PBO→ BKZ 160 mg Q4W a N=281 BKZ 160 mg Q4W N=431 ADA 40 mg Q2W N=140 † Ranked endpoints b ACR50 [NRI], – – – 28 189 (43.9) 64 &lt;0.001 101 196 66 n (%) -10 -45.7 (35.9) (45.5) -47.1 HAQ-DI CfB [MI], 0.89 0.82 0.86 −0.09 (0.03) −0.26 (0.02) −0.33 &lt;0.001 c −0.28 −0.30 −0.34 mean (SE) -0.04 -0.03 -0.05 (0.04) (0.03) (0.02) (0.05) PASI90 d [NRI], – – – 4 133 (61.3) f 28 &lt;0.001 86 (61.4) e 158 (72.8) f 32 n (%) (2.9) e (41.2) g (47.1) g SF-36 PCS CfB [MI], 36.9 38.1 37.6 2.3 6.3 6.8 &lt;0.001 c 6.2 7.3 7.3 mean (SE) -0.6 -0.5 -0.7 -0.5 -0.4 -0.8 -0.5 -0.4 -0.8 MDA [NRI], 5 14 1 37 194 63 &lt;0.001 106 209 67 n (%) -1.8 -3.2 -0.7 -13.2 (45.0) -45 (37.7) (48.5) -47.9 vdHmTSS CfB (subgroup ) h [MI], mean (SE) 15.67 (1.80) i 15.56 (1.69) j 17.39 (2.89) k 0.36 (0.10) i −0.01 (0.04) j −0.06 (0.08) k &lt;0.001 c – – – vdHmTSS CfB [MI],mean (SE) 13.31 (1.56) l 13.44 (1.47) m 14.55 (2.44) n 0.31 (0.09) l 0(0.04) m −0.03 (0.07) n 0.001 c – – – Other endpoints ACR20 [NRI], – – – 67 268 96 &lt;0.001 o 175 282 99 n (%) -23.8 (62.2) -68.6 (62.3) (65.4) -70.7 ACR70 [NRI], – – – 12 105 39 &lt;0.001 o 53 126 42 n (%) -4.3 (24.4) -27.9 -18.9 (29.2) -30 PASI100 d [NRI], – – – 3 103 f 14 &lt;0.001 o 60 122 26 n (%) (2.1) e (47.5) (20.6) g (42.9) e (56.2) f (38.2) g TJC CfB [MI], 17.1 16.8 17.5 −3.2 −10.0 −10.9 &lt;0.001 o −9.4 −11.5 −11.8 mean (SE) -0.7 -0.6 -1.1 (0.7) (0.5) -1 (0.7) (0.5) -0.9 SJC CfB [MI], 9.5 9 9.6 −3.0 (0.5) −6.6 (0.3) −7.5 &lt;0.001 o −6.8 (0.4) −7.2 (0.3) −7.9 mean (SE) -0.4 -0.3 -0.6 -0.6 -0.6 Randomised set. Interim results. †Reference arm; study not powered for statistical comparisons of ADA to BKZ or PBO. a PBO→BKZ pts received PBO to Wk 16, switched to BKZ 160 mg Q4W through Wk 24 (8 wks BKZ); b Resolution of enthesitis/dactylitis in pts with LEI&gt;0/LDI&gt;0 at BL pooled with BE COMPLETE (Wk 16 LEI=0 BKZ: 124/249 [49.8%], PBO: 37/106 [34.9%], p=0.008; LDI=0 BKZ: 68/90 [75.6%], PBO: 24/47 [51.1%], p=0.002); c Continuous outcome p values calculated with RBMI data; d Pts with PSO and ≥3% BSA at BL; e n=140; f n=217; g n=68; h Pts with hs-CRP ≥6 mg/L and/or bone erosion at BL; i n=221; j n=357; k n=108; l n=261; m n=416; n n=131; o Nominal, not powered for multiplicity. Conclusion Dual inhibition of IL-17A and IL-17F with BKZ in bDMARD-naïve pts with active PsA resulted in rapid, clinically relevant improvements in musculoskeletal and skin outcomes vs PBO. No new safety signals observed. 1,2 References [1]Ritchlin CT Lancet 2020;395(10222):427–40; 2. Coates LC Ann Rheum Dis 2021;80:779–80(POS1022). Disclosure of Interests Iain McInnes Consultant of: AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma, Grant/research support from: BMS, Boehringer Ingelheim, Celgene, Janssen, UCB Pharma, Laura Coates Consultant of: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Domain, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma, Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Robert B.M. Landewé Consultant of: Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Speakers bureau: Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Philip J Mease Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen and UCB Pharma, Yoshiya Tanaka Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Speakers bureau: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda, Akihiko Asahina Grant/research support from: AbbVie, Amgen, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, Sandoz and UCB Pharma, Alice B Gottlieb Consultant of: Amgen, AnaptsysBio, Avotres Therapeutics, Boehringer Ingelheim, BMS, Dermavant, Eli Lilly, Incyte, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and XBiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharma, UCB Pharma, and XBiotech: all funds go to Mount Sinai Medical School, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma, Paid instructor for: Astellas, DiCE, GSK, and Union, Grant/research support from: AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma, Barbara Ink Shareholder of: GSK, UCB Pharma, Employee of: UCB Pharma, Deepak Assudani Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jason Coarse Shareholder of: UCB Pharma, Employee of: UCB Pharma, Rajan Bajracharya Shareholder of: UCB Pharma, Employee of: UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Paid instructor for: Amgen, Abbvie, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma